Lee et al.

J Nanobiotechnol (2015) 13:54

DOI 10.1186/s12951-015-0118-0

REVIEW Open Access

Organic–inorganic hybrid nanoflowers:

types, characteristics, and future prospects
Seung Woo Lee1, Seon Ah Cheon1, Moon Il Kim2 and Tae Jung Park1* 

Abstract 
Organic–inorganic hybrid nanoflowers, a newly developed class of flower-like hybrid nanoparticles, have received
much attention due to their simple synthesis, high efficiency, and enzyme stabilizing ability. This article covers, in
detail, the types, structural features, mechanism of formation, and bio-related applications of hybrid nanoflowers. The
five major types of hybrid nanoflowers are discussed, i.e., copper–protein, calcium–protein, and manganese–protein
hybrid nanoflowers, copper–DNA hybrid nanoflowers, and capsular hybrid nanoflowers. The structural features of
these nanoflowers, such as size, shape, and protein ratio generally determine their applications. Thus, the specific
characteristics of hybrid nanoflowers are summarized in this review. The interfacial mechanism of nanoflower for-
mation is examined in three steps: first, combination of metal ion and organic matter; second, formation of petals;
third, growth of nanoflowers. The explanations provided herein can be utilized in the development of innovative
approaches for the synthesis of hybrid nanoflowers for prospective development of a plethora of hybrid nanoflowers.
The future prospects of hybrid nanoflowers in the biotechnology industry, medicine, sensing, and catalysis are also
discussed.
Keywords:  Biosynthesis, Nanoflowers, Organic–inorganic hybrid

Background structures of nanoflowers, and it is a formidable task to

Since the inceptive studies of new nanomaterials in the
early 2000s, various nanomaterials with captivating
morphologies such as the core–shell structure [1], and
Janus particle [2] have been developed. Among these
new nanostructures, the topographical features of nano-
flowers have piqued the interests of scientists because
the higher surface-to-volume ratio in comparison with
spherical nanoparticles is beneficial to enhancement in
the efficiency of surface reactions. Therefore, extensive
studies focusing on the applications of the nanoflow-
ers have been undertaken. Despite the increasing inter-
est in nanoflowers, synthesis of these species requires
very harsh conditions such as toxic organic solvents,
high temperature, and high pressure. Thus, it is difficult
to control their morphological features for tailoring the
*Correspondence: tjpark@cau.ac.kr
1
Department of Chemistry, Chung-Ang University, 84 Heukseok‑ro,
Dongjak‑gu, Seoul 06974, Republic of Korea
Full list of author information is available at the end of the article
apply these particles in the field of biochemistry.
Enzymes are biological species with excellent activity
and substrate specificity, but their use is limited by cer-
tain drawbacks such as high sensitivity to the surround-
ing environment, low reproducibility of experimental
outcomes, and the requirement for complex purifica-
tion processes. To facilitate application in drug delivery
systems or detectors, novel nanomaterials called “nano-
biomaterials” have been developed. These are also known
as “organic–inorganic hybrid nanomaterials;” the name
indicates that all of the inorganic nanoparticle compo-
nents are bound to organic materials. Current methods
for the preparation of nano-biomaterials can be classified
into four categories in terms of immobilization [3–6],
conjugation [7–9], crosslinking [10–13], and self-assem-
bly [14]. Nano-biomaterials have numerous prospective
applications in catalysis [15–18], biosensors [19–22], and
drug delivery [23–26].
Proteins as enzymes have a strong affinity for metal
ions as cofactor and thus, the stability of proteins is gen-
erally enhanced during immobilization onto the metal

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Lee et al. J Nanobiotechnol (2015) 13:54 Page 2 of 10

surface by the interaction such as charge affinity, covalent Types of nanoflowers

bond, and structural coupling [27, 28]. However, immobi- Hybrid nanoflowers can be classified on the basis of
lized proteins exhibit lower activity than the free enzyme, the structure of the particles and the type of metal and
primarily due to the loss of their activity by changing the organic material used. The classifications are summa-
orientation during the immobilization process and mass- rized in Table 1.
transfer limitations on solid supports [29–32]. Single-
protein nanoparticles and nanogels are examples of novel General nanoflowers using copper(II) ions and proteins
nano-biomaterials that have been used as catalysts with Since the initial development of hybrid nanoflowers con-
highly preserved activities [3, 10–13]. The activity of sisting of copper(II) ions and proteins, these species have
enzymes in these nanoparticles and nanogels could be as been intensively studied by focusing on their efficiency
much as ~60–90 % of that of the free enzymes. In one of and stability [35–39]. Because many studies on copper–
the few examples where the activity is better than that of protein hybrid nanoflowers have been investigated well
the free enzyme, organophosphorus hydrolase embedded than those of other hybrid nanoflowers, the synthesis
in mesoporous silica demonstrated an activity of ~200 % mechanism and applications of copper–protein hybrid
in solution compared with the free hydrolase [33]. In nanoflowers are relatively well understood.
the case of trypsin, which is a hydrolyzing enzyme that Ge et  al. [35] first serendipitously discovered the
can digest itself, its immobilization on a solid support hybrid nanoflower and confirmed that the copper ion
increased the catalytic efficiency by thousands of times and protein create a new type of particle via interaction.
compared with that of free trypsin [34]. However, prob- Subsequently, they synthesized four types of hybrid nano-
lems such as loss of enzyme properties are still encoun- flowers using α-lactalbumin, laccase, carbonic anhydrase,
tered in these complicated processes. and lipase, respectively. The synthesized hybrid nanoflow-
Recently, a new approach for facile and safe synthe- ers were used in the detection of phenols and oxidation
sis of hybrid nanomaterials was developed to overcome of catecholamines. Each efficiency of the nanoflowers was
the limitations of conventional methods [35]. Because it found to be the same or superior to (95–650 %) to those
is possible to fabricate a nanomaterial simply by adding
protein to metal ion solution, this synthetic method does
not require any toxic elements or extreme harsh condi- Table 1  Types of organic–inorganic hybrid nanoflowers
tions. Therefore, the organic substance involved in the Metal ion Organic material Target References
synthesis is subjected to less manipulation compared
1 Copper α-Lactalbumin – [35]
with other conventional methods to maintain the activity
Laccase Catecholamines,
of the immobilized enzyme. phenols
Carbonic anhy-
The flower-like hybrid nanomaterials generated by drase
this process are called “organic–inorganic hybrid nano- Lipase
flowers” or “hybrid nanoflowers”. Their synthesis mech-
2 Copper Laccase Phenol [36]
anism, physical properties, protein activity, stability,
3 Copper Glucose oxidase Glucose [37]
and reproducibility have been intensively studied, and and HRPa
thus far, these species have exhibited significantly bet- 4 Copper Trypsin HRPa, BSAb [38]
ter properties than the free enzymes. The feasibility of 5 Copper HRPa Hydrogen perox- [39]
in vivo application of nanoflowers in protein complexes, ide, phenol
medicines, and serological studies is also a topic of inves- 6 Calcium α-Amylase Cnp-G3c [44]
tigation. However, a new paradigm shift is required in 7 Calcium Chitosan Hydrogen per- [45]
application of hybrid nanoflowers from enzyme stability oxide
improvements and efficient drug delivery systems to new 8 Manganese Immunoglobulin G Ractopamine [46]
horizons such as cell imaging, biosensor, and medical Anti-ractopamine
ab
approaches.
Bovine serum
This review presents an overview of several synthetic albumin
strategies that have been suggested to diversify nano- 9 Copper DNA Specific cell [55]
flowers, including their structural features. Moreover, the 10 Copper Bovine liver Hydrogen per- [56]
synthesis mechanism is confirmed through analysis. On catalase oxide
the basis of experimental and theoretical data, we pro- a
  Horseradish peroxidase
pose future prospects for novel nanoflowers and their b
  Bovine serum albumin
further enhancement. c
 2-Chloro-4-nitrophenylmaltotrioside
Lee et al. J Nanobiotechnol (2015) 13:54 Page 3 of 10

Fig. 1  Application cycle of the membrane with incorporated laccase nanoflowers: fabrication, use, rinse, and reuse. Phenol and ortho-, meta-, and
para-substituted phenols react with 4-aminoantipyrine to form colored compounds, which can be easily detected. Reproduced with permission
from Ref. [36]: Copyright 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

of the conventional free enzyme solutions. The increased or result in reduced enzymatic activity, which limits the
efficiency is derived from the following interplay of fac- application of the hybrid materials. As an alternative,
tors: (i) the large surface area of the nanoflower which the discovery of this novel nanoflower offers a fast and
does not cause mass-transfer limitations; (ii) the coop- simple synthesis. The procedure used in this experiment
erative interaction of the entrapped enzyme molecules; (Fig. 2) is as follows: glucose oxidized by GOx generates
(iii) the mutual influence of the enzyme and the micro- H2O2, which is immediately catalyzed by HRP to oxi-
environment of the nanoflower that contains metal ions dize 3,3′,5,5′-tetramethylbenzidine (TMB), resulting in a
on each other (for example, Cu2+ ions in the nanoflowers color change from clear to blue. The conventional two-
may enhance the activity of laccase). step process generally does not lead to high efficiency
Furthermore, the researchers developed a simplified owing to the diffusion of H2O2 generated from glucose
phenol detector comprising a syringe filter contain- oxidation. However, in the hybrid nanoflower, loss of the
ing adsorbed hybrid nanoflowers of laccase [36] (Fig. 1). generated H2O2 can be reduced because GOx and HRP
Briefly, a mixture of aqueous phenol and 4-aminoantipy- are simultaneously present, resulting in more accurate
rine was injected into the nanoflower-coated filter using a detection.
syringe and kept in the filter chamber for 5 min. The high The trypsin hybrid nanoflower synthesized by Lin
activity of laccase entrapped in the nanoflowers enabled et  al. was used for enhanced protein analysis [38]. Mass
rapid oxidative interaction of phenol with 4-aminoanti- spectrometry (MS) used widely for proteomic analysis,
pyrine to generate antipyrine dyes. The final red solution
was pushed out of the syringe and collected for analysis
by naked-eye visualization or by using a UV/Vis spectro-
photometer. The detection rate of this method is faster
than that of pre-existing gas chromatography (GC) or
liquid chromatography (LC). This method also facilitated
the reuse of the filter for about 1 month through cleaning
due to the high stability of the enzyme in the particles.
Following this germinal research, Sun et  al. synthe-
sized multienzymatic hybrid nanoflowers using glucose
oxidase (GOx) and horse-radish peroxidase (HRP) [37],
demonstrating the possibility that two or more enzymes
could be included in a single hybrid nanoflower. Even to
date, most co-immobilizations of multi-enzyme are per-
formed via comparatively complicated processes such as
by covalent cross-linking [40], encapsulation [41], gene Fig. 2  The cascade enzymatic reaction of multi-enzyme co-embed-
ded hybrid nanoflower for glucose detection. Reproduced with
fusion [42], and post-translational enzyme conjugation
permission from Ref. [37]: Copyright 2014, Royal Society of Chemistry
[43]. Unfortunately, these techniques are time consuming
Lee et al. J Nanobiotechnol (2015) 13:54
involves analysis of enzymatically digested peptides cre-
ated from the parent protein. Therefore, effective prote-
olysis is required as a key step for effective identification
of proteins. Generally, proteolysis is performed by using
free enzymes, and suffers from some limitations such as
long digestion time, autolysis, low stability towards envi-
ronmental changes, and difficult recovery of products.
Enzymes immobilized on solid supports have been used
to overcome these disadvantages. The trypsin hybrid
nanoflower was first used as an immobilized enzyme by
Lin et  al. to achieve high proteolytic performance, good
enzyme stability and reusability, and a short digestion
time [38]. Moreover, the activity of the enzyme compo-
nent of the hybrid nanoflower was comparable to that
achieved in various conventional protein analyses. The
favorable results indicate that the hybrid nanoflower is a
promising enzyme system for proteomic analysis.
A hybrid nanoflower employing copper ions and HRP
for visual detection of hydrogen peroxide and phenol was
also synthesized [39]. As above, the hybrid nanoflower
was used as a catalyst in the reaction of hydrogen per-
oxide and phenol in the presence of 4-aminoantipyrine.
Changes in the solution color could be detected with
concentrations as low as 0.5 μM hydrogen peroxide and
1 μM phenol by the naked eye. The threshold concentra-
tion of hydrogen peroxide to prevent cellular damage is
50 μM; thus, the limit of detection (LOD) obtained with
the use of the hybrid nanoflower meets the requirement
for early clinical diagnosis. The LOD for phenol also sat-
isfies the requirements for application to the detection of
water pollution. In contrast, the LODs for hydrogen per-
oxide and phenol using free HRP were ~20 and ~10 μM,
respectively. The enzyme activity of the HRP hybrid
nanoflower is enhanced by the large surface-to-volume
ratio that facilitates contact with reactants. Moreover, the
reaction time of the HRP hybrid nanoflower (~5 min) is
faster than that of free HRP (~25 min). The above results
revealed that the hybrid nanoflower is more useful for the
development of a highly sensitive colorimetric sensing
platform.
General nanoflowers using calcium(II) ions and proteins
Nanoflowers employing calcium ions have also been
investigated, even though most nanoflowers are synthe-
sized with the copper ion [44, 45]. A nanoflower employ-
ing calcium phosphate crystals was synthesized by Wang
et  al. by using the same method used for the synthesis
of copper nanoflowers [44]. The flower-like morphol-
ogy was confirmed and a postulate of how the activity
increases due to the enzyme immobilization procedure
was presented. The α-amylase used in this experiment is
an enzyme that exhibits allosteric phenomena (Fig.  3a).
In the absence of calcium ions, α-amylases are usually
Page 4 of 10
Fig. 3  a Allosteric effect of α-amylase: α-amylase changes from
inactive form to active form by binding calcium ion to allosteric site
in inactive α-amylase and b α-amylase immobilized in nanocrystals.
Reproduced with permission from Ref. [44]: Copyright 2013, American
Chemical Society
in an inactive state as the functional site is inhibited.
In contrast, in the presence of calcium ions, the allos-
teric sites of α-amylase are occupied by the calcium ion,
thus affecting the structure of the functional site. Dur-
ing the synthesis of the hybrid nanoflower using calcium
ions and α-amylase, the calcium ions activate and are
strongly bound to α-amylase. Because the two elements
are located close to each other during the formation of
the hybrid nanoflower, α-amylase was active for a longer
period than the free enzyme, which is randomly and
briefly activated by calcium ions (Fig.  3b). Thus, Wang
et al. showed that it is essential to understand the chemi-
cal interaction between the protein and nanomaterials to
improve the functionality of the protein in a given envi-
ronment [44].
A hybrid nanoflower employing calcium ions was also
presented in a recent study [45]. Unlike previous syn-
thesis methods using protein solution, chitosan (CS)
and tripolyphosphate (TPP) were used to fabricate a gel-
form composite via ionic bonding. Although this method
has different steps from that used by Hou et al. [44], the
mechanism of nanoflower formation is the same (Fig. 4).
Calcium ions and TPP form calcium phosphate crystals,
and the nanoflower is obtained by the reaction of these
crystals and the CS-TPP gel complex. Almost any type
of catalyst could be used in this experiment because the
catalyst combines with chitosan in the CS-TPP gel com-
plex by electrostatic interaction. However, because addi-
tion of the catalyst declined in the nucleation sites for
calcium phosphate formation, it should be noted that the
maximum amount of catalyst for the formation of the
nanoflower was 5.0  mg. This technique for nanoflower
synthesis provides a new approach that facilitates the
Lee et al. J Nanobiotechnol (2015) 13:54
Fig. 4  Schematic synthesis of chitosan–calcium ion hybrid nanoflower. Chitosan binds to pyrophosphate through ionotropic gelation and gener-
ates CS-TPP gel complex which reacts with calcium phosphate crystal to form hybrid nanoflower. Reproduced with permission from Ref. [45]:
Copyright 2014, American Chemical Society
generation of the nanoflower using a variety of organic
substances.
General nanoflowers using manganese(II) ions and proteins
Manganese phosphate hybrid nanoflowers were syn-
thesized by Zhang et  al. to apply into a novel electro-
chemical biosensor for detection of ractopamine, which
can cause acute poisoning consumed by humans [46].
Although many analytical methods have been devel-
oped for the detection of ractopamine, such as liquid
chromatography–mass spectrometry (LC–MS) [47,
48], gas chromatography–mass spectrometry (GC–
MS) [49], high-performance liquid chromatography
(HPLC) [50], and bioassay [51]. They have some limits
owing to high instrument cost and long-time analysis.
To solve the problem, electrochemical methods were
applied by using the phenolic hydroxyl group, which
makes ractopamine electrochemically active [52]. How-
ever, this detection method was also limited that due to
its low response activity on electrode surfaces. Hybrid
nanoflower as a novel electrochemical biosensor over-
comes the disadvantage. These nanoflowers are made by
manganese(II) ions and three types of protein, immu-
noglobulin G (IgG), ractopamine antibody (RACanti),
and bovine serum albumin (BSA) (Fig.  5). The detec-
tion limits of the developed electrochemical biosensors
were 4.6, 9.32, and 26 pg mL−1, respectively. Compared
with the detection limits of previous different methods,
these results present that electrochemical methods using
Page 5 of 10
hybrid nanoflowers are more sensitive [52–54]. This
study shows that the hybrid nanoflower can be used as
electrochemical tools as well as catalyst or drug delivery
matter.
General nanoflowers using copper(II) ion and DNA
Hu et  al. used DNA as the organic material instead of
protein in hybrid nanoflowers [55]. Because DNA is
highly soluble in aqueous medium and has a high content
of nitrogen atoms in its structure like protein, it could
be used in the synthesis of hybrid nanoflowers by bind-
ing metal ions. The DNA hybrid nanoflower morphology
was combined with the fluorescence resonance energy
transfer (FRET) phenomenon to obtain high-resolution
images of cells or to use for traceable drug delivery sys-
tems. In brief, the researchers created a site in the DNA
template for the simultaneous attachment of a drug and
fluorescent dyes (FAM, CY3, ROX), and subsequently,
they synthesized a hybrid nanoflower coupled to the
fabricated DNA by rolling circle replication (RCR) with
the metal ions (Fig.  6). Consequently, they were able to
obtain a high-resolution image based on FRET between
the dyes using long-wavelength light, which does not
affect the cells. Furthermore, the path of drug delivery in
the living cells was successfully traced by monitoring the
light emitted by the dyes. Thus, Hu et al. suggested that
DNA hybrid nanoflowers can be applied in many fields
by showing the feasibility of the synthesis of DNA hybrid
nanoflowers [55].
Lee et al. J Nanobiotechnol (2015) 13:54 Page 6 of 10

Fig. 5  Schematic representation of the synthesis of manganese-based hybrid nanoflowers as a novel electrochemical biosensor for the detection
of ractopamine, including (i) Mn3(PO4)2-IgG, (ii) Mn3(PO4)2-RACanti (anti-ractopamine antibody), and (iii) Mn3(PO4)2-BSA-Au nanoflowers. Reproduced
with permission from Ref. [46]: Copyright 2015, Elsevier

Fig. 6  Sequence-independent self-assembly of multicolor FRET (fluorescence resonance energy transfer) DNA hybrid nanoflower. Reproduced with
permission from Ref. [55]: Copyright 2014, Wiley-VCH Verlag

Capsular nanoflowers using copper(II) ions and proteins
A capsular nanoflower was synthesized by Jiang and co-
workers, as shown in Fig. 7 [56, 57]. Compared with early
hybrid nanoflowers synthesized from a metal phosphate
and protein, the capsular nanoflower was synthesized by
an additional wrapping with protamine and silica through
a biomimetic mineralization approach and removing the
metal from the core. Because the rough surface of the mul-
tiple shells facilitates the adsorption of substrates, the cap-
sular nanoflower exhibited significantly enhanced enzyme
activity as well as better stability under extreme conditions
(high temperature, pH, long-term storage) than simple
hybrid nanoflowers. These properties provide a practi-
cable and useful solution for enhancing the efficiency in
bio-chemical applications such as catalysis and drug
delivery.
Characteristics
Structural features and enzyme efficiency
As shown in Table 2, the hybrid nanoflowers can be clas-
sified based on characteristics such as shape, size, pro-
tein/total weight ratio percent, and enzyme efficiency
compared to that of the free enzyme.
Although the size of hybrid nanoflowers varies depend-
ing on the protein concentration, the range of variation is
narrow (about ±3 μm). Thus, based on the average size
from optimized data, the nanoflowers range from 2 to
30  μm, and the pore size (which is the diameter of the
Lee et al. J Nanobiotechnol (2015) 13:54
Fig. 7  Scheme of preparation procedure of the FPSH capsules: a formation of protein–inorganic hybrid microflowers; b formation of (protamine-
silica)2 bilayers on the microflowers; c formation of the FPSH capsules after eliminating the microflower template through EDTA treatment. Repro-
duced with permission from Ref. [56]: Copyright 2014, The Royal Society of Chemistry
hole between petals) is approximately 0.1  μm. Because
the size of most of these hybrid flowers is expressed in
micro units (μm), we believe that the use of the term
“microflower” is more correct than “nanoflower.” In addi-
tion, the shape of the hybrid nanoflowers is similar to
that of round flowers, but with subtle variations. Thus,
the pictures that resembles the respective scanning elec-
tron microscopy (SEM) images are provided to highlight
the differences (Table 2).
The weight ratio of protein to total particle weight
measured by thermogravimetric analysis (TGA) is also
summarized in Table  2, demonstrating that the protein
constitutes 10–66 % of the total weight. Furthermore, as
more protein is used, the percentage of protein increases.
However, the encapsulation efficiency (the ratio of the
amount of immobilized protein to the total amount of
protein employed) follows a completely opposite trend.
Excessive addition of protein to a constant weight of
inorganic component induces a dramatic decrease of the
encapsulation efficiency. In light of these considerations,
the proper amount of protein must be selected to con-
serve the protein and to attain good morphology and a
high weight percentage.
Finally, we consider the enzyme efficiency of hybrid
nanoflowers. Compared with the corresponding free
enzyme solutions, the enzyme efficiency of hybrid nano-
flowers varies from 85 to over 1000 %. These results sug-
gest that the proteins in hybrid nanoflowers have higher
activity and stability than the corresponding free enzyme
solutions despite immobilization in the flower petals.
Moreover, hybrid nanoflowers overcome the previously
encountered problem of mass-transfer limitation and
open up an avenue for application to various research
and detection fields.
Page 7 of 10
Mechanism
The mechanism for the synthesis of organic–inorganic
hybrid nanoflowers comprises three steps (Fig.  8). In
the early growth step, primary crystals of metal phos-
phate [M3(PO4)2, (M: Cu, Ca)] are formed. At this stage,
the organic molecules (protein, DNA) form complexes
with the metal ions (Cu2+, Ca2+), mainly through coor-
dination via the amide groups in the protein backbone.
These complexes provide a location for nucleation of the
primary crystals. In the second growth stage, metal-pro-
tein crystals aggregate into large agglomerates of protein
molecules and primary petals are formed. The kinetically
controlled growth of metal phosphate crystals originates
on the surfaces that have the Cu2+ binding sites of these
agglomerates, causing flower-like petals to appear in the
embryo. In the final step, anisotropic growth leads to
complete formation of a branched flower-like structure.
In this growth process, the protein induces nucleation of
the metal phosphate crystals to form the scaffold for the
petals and serves as a “glue” to bind the petals together. In
the absence of the proteins, large crystals, but no nano-
flowers, are formed.
Future prospects
In the 1960s, the development of enzyme immobilization
technology inspired chemists to design new biomaterials
containing highly stabilized enzymes. However, immo-
bilization generally led to loss of the enzyme activity. By
the 1990s, the activity of enzymes immobilized on nano-
sized materials could be maintained at levels up to that
of the free enzymes. Interest in this field was again awak-
ened with the unearthing of the first organic–inorganic
hybrid nanoflower in 2012, and many studies focusing on
new flower-like hybrid nanomaterials are still in progress.
Lee et al. J Nanobiotechnol (2015) 13:54 Page 8 of 10

Table 2  Characteristics of organic–inorganic hybrid nanoflowers

Size Refer
Shape SEM image Protein ratio Enzyme efficiency
(μm) ences
Laccase: 650%
Carbonic anhydrase:
1 3 – [35]
260%
Lipase: 95%

2 20 – GOx & HRP: 400% [37]

3 27 3 9~12.6% Trypsin: 270% [38]

4 17 17.2% HRP: 506% [39]

5 4 0.5 20.16% α-Amylase: 1000% [44]

6 4 1 25.6% Catalase: 85% [45]

7 2 – – [55]

FPSH :
8 10 27.2% Catalase: 11% [56]
PSH : 66.5%
a
 Rose
b
  Blue ball
c
 Peony
d
 Satin
e
  Water flower
f
 Zonal
g
  Viburnum opulus
h
 Marigolds

Future research for the development of drug delivery
systems, biosensors, biocatalysts, and bio-related devices
is anticipated to take multiple directions. New synthesis
principles, new types of hybrid nanoflowers, and detailed
mechanisms are expected to emerge. The application of
nanoflowers in bio-catalysis and enzyme mimetics, tis-
sue engineering, and the design of highly sensitive bio-
sensing kits, as well as industrial bio-related devices with
advanced functions, various and controllable syntheses,
biocompatibility, and modifications of hybrid nanoflower
structures and properties, should receive increasing
attention.
Conclusions
In summary, organic–inorganic hybrid nanoflowers
have piqued the interest of researches and numerous
related papers have been published. Research in this
field is spurred by the simplicity of the synthesis and safe
Lee et al. J Nanobiotechnol (2015) 13:54
Fig. 8  Synthesis mechanism of organic–inorganic hybrid nanoflower. Reproduced with permission from Ref. [35]: Copyright 2012, Nature Publish-
ing Group
conditions. Moreover, high efficiency and enzyme sta-
bility are readily achieved with hybrid nanoflowers. We
believe that the study of organic–inorganic hybrid nano-
flowers will lead to creative solutions and rapid develop-
ment of biomaterials and biotechnology industries.
Abbreviations
GOx: glucose oxidase; HRP: horse-radish peroxidase; LOD: limit of detection;
CS: chitosan; TPP: tripolyphosphate; SEM: scanning electron microscopy.
Authors’ contributions
SWL and TJP conceived the idea of the work and performed the check-
ing the cited references. SAC and MIK were reviewed and commented the
manuscript. All authors contributed to the preparation of the manuscript
and commented on the final version. All authors read and approved the final
manuscript.
Author details
1
 Department of Chemistry, Chung-Ang University, 84 Heukseok‑ro,
Dongjak‑gu, Seoul 06974, Republic of Korea. 2 Department of BioNano Tech-
nology, Gachon University, 1342 Seongnamdaero, Sujeong‑gu, Seongnam‑si,
Gyeonggi‑do 461‑701, Republic of Korea.
Acknowledgements
This research was supported by the Advanced Production Technology Devel-
opment Program, Ministry of Agriculture, Food and Rural Affairs (312066-3),
a grant of the Korean Health Technology R&D Project, Ministry of Health &
Welfare, Republic of Korea (HI13C0862) and the Chung-Ang University Gradu-
ate Research Scholarship in 2015.
Compliance with ethical guidelines
Competing interests
The authors declare that they have no competing interests.
Received: 5 August 2015 Accepted: 25 August 2015
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